We propose to continue our attempt to identify phenotypic alterations (or their patterns) which are related to crucial events during carcinogenic evolution. A comparison between these events as induced by diethylnitrosamine (an alkylating agent) and fluorenylacetamide (an aromatic amide) will continue. In addition to using morphologic, chromosomal, and alpha fetoprotein levels as measurements, we will include analysis of repair mechanisms and DNA alteration. We will utilize two carcinogens of different chemical classes: 1) diethylnitrosamine, an alkylating agent; 2) N-2-fluorenylacetamide, an aromatic amide. We will attempt to correlate alterations in three modalities with the crucial sequences in malignant evolution; a) morphology - light and electron microscopy, histochemistry; b) chromosomal composition; c) alpha fetoprotein production. In addition, we will continue to examine and expand our investigation of the capacity of carcinogen-exposed tissues to "activate" carcinogens as evidenced by mutagenic capacity. Further studies of the alteration of DNA by base-analysis will be pursued using HPLC technology. Each of these modalities may give information concerning alteration of DNA as related to the "phases" described by biologic means.